The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
A Fatty Acid Synthase Blockade Induces Tumor Cell-cycle Arrest by Down-regulating Skp2
Open accessAbstract
In eukaryotes, fatty acid synthase (FAS) is the enzyme responsible for synthesis of palmitate, the precursor of long-chain nonessential fatty acids. FAS is up-regulated in a wide range of cancers and has been suggested as a relevant drug target. Here, two independent approaches are taken toward knocking down FAS and then probing its connection to tumor cell proliferation. In one approach, Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS. In a separate strategy, the expression of FAS is suppressed by targeted knock-down with small interfering RNA. In both circumstances, the ablation of FAS activity causes a dramatic down-regulation of Skp2, a component of the E3 ubiquitin ligase that controls the turnover of p27Kip1. These effects ultimately tie into the retinoblastoma protein pathway and lead to a cell-cycle arrest at the G1/S boundary. Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins.
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“FASN can promote cancer progression and contribute to therapy resistance by sustaining mitogenic signaling, facilitating the G1/S transition, and supplying lipid resources necessary for biomass accumulation and evasion of cell cycle checkpoints [30,48].”
From Inhibition of fatty acid synthase enhances therapeutic efficacy and delays acquired resistance to BRAF-targeted therapy in colorectal cancer (2026) · cites this paper as [48]
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Cites
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
Carrano, A. C., Eytan, E., Hershko, A., & Pagano, M. (1999) · Nature Cell Biology · doi:10.1038/12013 · Cited by 1,544
Activity-based protein profiling: The serine hydrolases
Liu, Y., Patricelli, M. P., & Cravatt, B. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14694 · Cited by 1,143
Weir, H. K. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djg040 · Cited by 864
Fatty acid synthesis: a potential selective target for antineoplastic therapy
Kuhajda, F. P., Jenner, K., Wood, F. D., Hennigar, R. A., Jacobs, L. B., Dick, J. D., & Pasternack, G. R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6379 · Cited by 705
Insights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex
Schulman, B. A., Carrano, A. C., Jeffrey, P. D., Bowen, Z., Kinnucan, E., Finnin, M. S., Elledge, S. J., Harper, J. W., Pagano, M., & Pavletich, N. P. (2000) · Nature · doi:10.1038/35042620 · Cited by 610
Orlistat Is a Novel Inhibitor of Fatty Acid Synthase with Antitumor Activity
Kridel, S. J., Axelrod, F. T., Rozenkrantz, N., & Smith, J. W. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3645 · Cited by 610
Self-citationSynthesis and antitumor activity of an inhibitor of fatty acid synthase
Kuhajda, F. P., Pizer, E. S., Li, J. N., Mani, N. S., Frehywot, G. L., & Townsend, C. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3450 · Cited by 568
Profiling Serine Hydrolase Activities in Complex Proteomes
Kidd, D., Liu, Y., & Cravatt, B. F. (2001) · Biochemistry · doi:10.1021/bi002579j · Cited by 369
Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma.
Milgraum, L. Z., Witters, L. A., Pasternack, G. R., & Kuhajda, F. P. (1997) · PubMed · Cited by 333
Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells.
Pizer, E. S., Jackisch, C., Wood, F. D., Pasternack, G. R., Davidson, N. E., & Kuhajda, F. P. (1996) · PubMed · Cited by 291
Research works printed but not linked: 7
- Milgraum, 1997, Clin. Cancer Res., 3, 2115
- Furuya, 1997, Anticancer Res., 17, 4589
- Pizer, 1996, Cancer Res., 56, 2745
- Pizer, 1998, Cancer Res., 58, 4611
- Li, 2001, Cancer Res., 61, 1493
- Pizer, 1996, Cancer Res., 56, 745
- Yang, 2002, Clin. Cancer Res., 8, 3419
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Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis
Menendez, J. A., & Lupu, R. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2222 · Cited by 2,941
Targeting cellular metabolism to improve cancer therapeutics
Zhao, Y., Butler, E. B., & Tan, M. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.60 · Cited by 1,010
Fatty Acid Synthase As a Potential Therapeutic Target in Cancer
Flavin, R., Peluso, S., Nguyen, P. L., & Loda, M. F. (2010) · Future Oncology · doi:10.2217/fon.10.11 · Cited by 545
Disruption of Hepatic Adipogenesis Is Associated With Impaired Liver Regeneration in Mice
Shteyer, E., Liao, Y., Muglia, L. J., Hruz, P. W., & Rudnick, D. A. (2004) · Hepatology · doi:10.1002/hep.20462 · Cited by 234
Yang, P., Liu, K., Ngai, M. H., Lear, M. J., Wenk, M. R., & Yao, S. Q. (2009) · Journal of the American Chemical Society · doi:10.1021/ja907716f · Cited by 235
Metadata
- Authors
- Knowles, L. M., Axelrod, F., Browne, C. D., & Smith, J. W.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Smith, Jeffrey W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 29
- Pages
- 30540-30545
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2115307821
- Cited by
- 146
- References
- 38
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 4 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 12 · 2013: 6 · 2012: 13
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA30199, CA-69306, R01CA069306, CA6982713, P30CA030199)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- fatty acid synthase, Skp2, orlistat, cell cycle arrest, G1/S checkpoint, p27, ubiquitin-mediated proteolysis, E3 ubiquitin ligase, tumor cell proliferation, siRNA knockdown, cancer drug targets
- MeSH terms
- Orlistat, Avidin, Biotin, Cell Cycle, Cell Division, Cell Line, Dose-Response Relationship, Drug, Epithelial Cells, Fatty Acids, Humans, Lactones, Lipase, Obesity, Serine Endopeptidases, Time Factors, Blotting, Western, Down-Regulation, Retinoblastoma Protein, G1 Phase, S Phase, Cell Cycle Proteins, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Palmitic Acid, Tumor Suppressor Proteins, Ubiquitin, RNA, Small Interfering, Ubiquitin-Protein Ligases, S-Phase Kinase-Associated Proteins, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27, Fatty Acid Synthases
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